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Related Experiment Videos

A Na(+)-dependent nucleoside transporter in microglia.

M Hong1, L Schlichter, R Bendayan

  • 1Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada.

The Journal of Pharmacology and Experimental Therapeutics
|December 22, 1999
PubMed
Summary

Rat microglia cells possess a sodium-dependent nucleoside transport system. This system is crucial for understanding how antiretroviral drugs like zidovudine interact with nucleosides in the brain.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • HIV-1 targets macrophages and microglia in the central nervous system.
  • Nucleoside analog drugs, such as zidovudine, improve neurological function in HIV-1 patients.
  • Carrier-mediated transport systems are vital for nucleoside and nucleoside analog drug uptake.

Purpose of the Study:

  • To characterize thymidine uptake in rat microglia (MLS-9) cells.
  • To investigate the role of sodium (Na+) in nucleoside transport.
  • To determine the interaction of nucleoside analogs with the microglia transport system.

Main Methods:

  • Utilized a continuous rat microglia cell line (MLS-9) grown as a monolayer.
  • Measured thymidine uptake under varying sodium concentrations.

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  • Performed kinetic analysis and competitive inhibition studies with nucleoside probes and analog drugs.

    • Main Results:

    • Approximately 50% of thymidine uptake was Na+-dependent.
    • A single saturation system for thymidine uptake was identified (K(m) = 44 microM at 37°C) with a 2:1 Na+/thymidine stoichiometry.
    • Nucleoside analogs, particularly zidovudine (IC(50) = 0.6 microM), significantly inhibited thymidine uptake non-competitively.

    Conclusions:

    • Rat microglia express a Na+-dependent nucleoside transport system.
    • Antiretroviral nucleoside analog drugs may interact with nucleoside transporters in microglia.
    • Findings provide insights into drug delivery mechanisms for HIV-1 associated neurocognitive disorders.